The Impact of Socioeconomic Conditions on Chronic Chagas Disease Progression

Background: We observed that mitochondrial reactive oxygen species (mtROS) plays very important roles in the pregression of chagesic disease (CD). In this study, we utilized genetically-modified mice to scavenge mtROS to investigate the impact of improved ROS scavenging capacity on heart function in CD. Methods and Results: C57BL/6 mice (wild-type, MnSODtg, MnSOD+/-) were infected with Trypanosoma cruzi(Tc). Chronically infected mice (≥120dpi) exhibited a substantial decrease in heart tissue MnSOD gene expression, protein level, enzyme activity and antioxidant level; decrease of heart dysfunction via lower of SV, CO, EF, FS and LVPW,s, and increase of ESV/EDS and LVID;s; enhancement of hypertrophy by increase of IVS, LV mass and areas duo to augmentation of collagen expressions. One of our novel observations was that sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) lost its role of maintenance of low cytoplasm free calcium and mediated calcium uptake to intracellular store in Tc-induced chronic chagasic disease. Studies of fresh heart slices using O2K confirmed that Tc diminished heart mitochondrial function like decrease of oxygen flux and respiratory control ratio (RCR), which were caused by enhancements of ROS. Myocardial mitochondrial damage was pronounced and associated with a >x% decline in mitochondrial oxygen flux in chronically infected wild-type and MnSOD transgenic mice. Imaging of intact heart for cardiomyocytes and collagen by the nonlinear optical microscopy techniques showed significant increase in collagen (>x0-fold) in chronically infected wild-type mice; while MnSODtg mice exhibited a basal increase in collagen that did not change during chronic phase. Chronically infected MnSODtg mice exhibited a marginal decline in Tc-induced heart function, heart hypertrophy, mitochondrial dysfunction Conclusions: Overexpression of MnSOD inhibited Tc-induced oxidative damage od heart tissue. , suggesting that enhancing the mitochondrial ROS scavenging capacity was beneficial in controlling the inflammatory and oxidative pathology, and cardiac remodeling responses that are hallmarks of chronic Chagas disease.

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Benznidazole decreases the risk of chronic Chagas disease progression and cardiovascular events: A long-term follow up study

EClinicalMedicine ◽

10.1016/j.eclinm.2020.100694 ◽

2020 ◽

pp. 100694

Author(s):

Alejandro M. Hasslocher-Moreno ◽

Roberto M. Saraiva ◽

Luiz H.C. Sangenis ◽

Sergio S. Xavier ◽

Andrea S. de Sousa ◽

...

Keyword(s):

Disease Progression ◽

Chagas Disease ◽

Cardiovascular Events ◽

Follow Up Study ◽

Long Term Follow Up ◽

Chronic Chagas Disease

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Predictors of development of cardiac and digestive disorders among patients with indeterminate chronic Chagas Disease

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009680 ◽

2021 ◽

Vol 15 (8) ◽

pp. e0009680

Author(s):

Erika Alessandra Pellison Nunes da Costa ◽

Cassiano Victória ◽

Carlos Magno Castelo Branco Fortaleza

Keyword(s):

Chagas Disease ◽

Cox Regression ◽

Female Gender ◽

Southeastern Brazil ◽

Coronary Syndrome ◽

Final Multivariable Model ◽

Cardiac Disorders ◽

Digestive Disorders ◽

The Impact ◽

Chronic Chagas Disease

American trypanosomiasis (Chagas disease, CD) affects circa 7 million persons worldwide. While of those persons present the asymptomatic, indeterminate chronic form (ICF), many will eventually progress to cardiac or digestive disorders. We studied a nonconcurrent (retrospective) cohort of patients attending an outpatient CD clinic in Southeastern Brazil, who were admitted while presenting the ICF in the period from 1998 through 2018 and followed until 2019. The outcomes of interest were the progression to cardiac or digestive CD forms. We were also interested in analyzing the impact of Benznidazole therapy on the progression of the disease. Extensive review of medical charts and laboratory files was conducted, collecting data up to year 2019. Demographics (upon inclusion), body mass index, comorbidities (including the Charlson index) and use of Benznidazole were recorded. The outcomes were defined by abnormalities in those test that could not be attributed to other causes. Statistical analysis included univariate and multivariable Cox regression models. Among 379 subjects included in the study, 87 (22.9%) and 100 (26.4%) progressed to cardiac and digestive forms, respectively. In the final multivariable model, cardiac disorders were positively associated with previous coronary syndrome (Hazzard Ratio [HR], 2.42; 95% Confidence Interval [CI], 1.53–3.81) and negatively associated with Benznidazole therapy (HR, 0.26; 95%CI, 0.11–0.60). On the other hand, female gender was the only independent predictor of progression to digestive forms (HR, 1.56; 95%CI, 1.03–2.38). Our results point to the impact of comorbidities on progression do cardiac CD, with possible benefit of the use of Benznidazole.

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Faculty Opinions recommendation of Drug-induced cure drives conversion to a stable and protective CD8+ T central memory response in chronic Chagas disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1107065.576411 ◽

2008 ◽

Author(s):

Thomas W von Geldern

Keyword(s):

Chagas Disease ◽

Central Memory ◽

Drug Induced ◽

Memory Response ◽

Chronic Chagas Disease

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Constructing Identity in “Glocal” Politics

American Journal of Islam and Society ◽

10.35632/ajis.v15i3.2174 ◽

1998 ◽

Vol 15 (3) ◽

pp. 81-106

Author(s):

M. A. Muqtedar Khan

Keyword(s):

Cold War ◽

International Relations ◽

World Politics ◽

Socioeconomic Conditions ◽

Post Cold War ◽

Important Concept ◽

Construction Of Identity ◽

The World ◽

The Impact ◽

The Relationship

This paper seeks to understand the impact of current global politicaland socioeconomic conditions on the construction of identity. I advancean argument based on a two-step logic. First, I challenge the characterizationof current socioeconomic conditions as one of globalization bymarshaling arguments and evidence that strongly suggest that along withglobalization, there are simultaneous processes of localization proliferatingin the world today. I contend that current conditions are indicative ofthings far exceeding the scope of globalization and that they can bedescribed more accurately as ccglocalization.~H’2a ving established thisclaim, I show how the processes of glocalization affect the constructionof Muslim identity.Why do I explore the relationship between glocalization and identityconstruction? Because it is significant. Those conversant with current theoreticaldebates within the discipline of international relations’ are awarethat identity has emerged as a significant explanatory construct in internationalrelations theory in the post-Cold War era.4 In this article, I discussthe emergence of identity as an important concept in world politics.The contemporary field of international relations is defined by threephilosophically distinct research programs? rationalists: constructivists,’and interpretivists.’ The moot issue is essentially a search for the mostimportant variable that can help explain or understand the behavior ofinternational actors and subsequently explain the nature of world politicsin order to minimize war and maximize peace.Rationalists contend that actors are basically rational actors who seekthe maximization of their interests, interests being understood primarilyin material terms and often calculated by utility functions maximizinggiven preferences? Interpretivists include postmodernists, critical theorists,and feminists, all of whom argue that basically the extant worldpolitical praxis or discourses “constitute” international agents and therebydetermine their actions, even as they reproduce world politics by ...

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Treatment of HIV-associated facial lipoatrophy: impact on infection progression assessed by viral load and CD4 count

Anais Brasileiros de Dermatologia ◽

10.1590/abd1806-4841.2013895 ◽

2013 ◽

Vol 88 (4) ◽

pp. 570-577 ◽

Cited By ~ 5

Author(s):

Flávia Machado Gonçalves Soares ◽

Izelda Maria Carvalho Costa

Keyword(s):

Viral Load ◽

Disease Progression ◽

Statistical Significance ◽

Undetectable Viral Load ◽

Fat Distribution ◽

Cd4 Count ◽

Before And After ◽

Facial Lipoatrophy ◽

A Prospective Study ◽

The Impact

BACKGROUND: HIV/AIDS-Associated Lipodystrophy Syndrome includes changes in body fat distribution, with or without metabolic changes. The loss of fat from the face, called facial lipoatrophy, is one of the most stigmatizing signs of the syndrome.OBJECTIVES:To evaluate the effect of FL treatment using polymethylmethacrylate (PMMA) implants on disease progression, assessed by viral load and CD4 cell count.METHODS: This was a prospective study of 44 patients treated from July 2009 to December 2010. Male and female patients, aged over 18 years, with clinically detectable FL and who had never been treated were included in the study. PMMA implantation was done to fill atrophic areas. Laboratory tests were conducted to measure viral load and CD4 count before and after treatment.RESULTS: Of the 44 patients, 72.72% were male and 27.27% female, mean age of 44.38 years. Before treatment, 82% of patients had undetectable viral load, which increased to 88.6% after treatment, but without statistical significance (p = 0.67). CD4 count before treatment ranged from 209 to 1293, averaging 493.97. After treatment, the average increased to 548.61. The increase in CD4 count after treatment was statistically significant with p = 0.02.CONCLUSION: The treatment of FL with PMMA implants showed a statistically significant increase in CD4 count after treatment, revealing the impact of FL treatment on disease progression. Viral load before and after treatment did not vary significantly.

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Natural History of NAFLD

Journal of Clinical Medicine ◽

10.3390/jcm10061161 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1161

Author(s):

Raluca Pais ◽

Thomas Maurel

Keyword(s):

Liver Disease ◽

Natural History ◽

Disease Progression ◽

Specific Treatment ◽

Alcoholic Fatty Liver ◽

Individual Level ◽

Close Relationship ◽

History Of ◽

The Individual ◽

The Impact

The epidemiology and the current burden of chronic liver disease are changing globally, with non-alcoholic fatty liver disease (NAFLD) becoming the most frequent cause of liver disease in close relationship with the global epidemics of obesity, type 2 diabetes and metabolic syndrome. The clinical phenotypes of NAFLD are very heterogeneous in relationship with multiple pathways involved in the disease progression. In the absence of a specific treatment for non-alcoholic steatohepatitis (NASH), it is important to understand the natural history of the disease, to identify and to optimize the control of factors that are involved in disease progression. In this paper we propose a critical analysis of factors that are involved in the progression of the liver damage and the occurrence of extra-hepatic complications (cardiovascular diseases, extra hepatic cancer) in patients with NAFLD. We also briefly discuss the impact of the heterogeneity of the clinical phenotype of NAFLD on the clinical practice globally and at the individual level.

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